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首页> 外文期刊>Journal of pharmaceutical sciences. >Thiol exchange: an in vitro assay that predicts the efficacy of novel homocysteine lowering therapies.
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Thiol exchange: an in vitro assay that predicts the efficacy of novel homocysteine lowering therapies.

机译：硫醇交换：一种体外试验，预测新型降低同型半胱氨酸疗法的功效。

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Elevated plasma total homocysteine (tHcy) is a risk factor for atherosclerosis. Hcy is 70-80% bound to albumin as a disulfide. Recent trials have evaluated ability of thiol-containing drugs to exchange with protein bound Hcy and consequently increase its renal clearance. The objective of this study was to develop an in vitro assay to predict the efficacy of thiol-containing drugs to lower tHcy in the clinical setting. The assay was used to test the effects of N-acetylcysteine (NAC), mesna, captopril, dimercaptosuccinic acid (DMSA), and penicillamine. Hcy was added in vitro to plasma of healthy subjects (n = 6) and equilibrated. Concentrations of thiol exchange agent were added and incubated at 37 degrees C. Aliquots were removed at selected intervals and free Hcy determined. Mesna, captopril, and NAC caused a concentration-dependent increase in free Hcy. Three-hundred micromolar mesna and captopril had a greater effect than equimolar NAC, increasing free Hcy by 33.9 +/- 5.0% and 32.0 +/- 2.6%, respectively compared to 22.3 +/- 2.4% for NAC, p < 0.001. Our in vitro results indicate that mesna, captopril, and NAC effectively exchange with covalently bound Hcy. This assay can act as screening tool for novel tHcy lowering therapies and should spare the expense of negative trials.
机译：血浆总同型半胱氨酸（tHcy）升高是动脉粥样硬化的危险因素。 Hcy与白蛋白结合为二硫化物，占70-80％。最近的试验已经评估了含硫醇的药物与结合蛋白的Hcy交换的能力，从而增加了其肾脏清除率。这项研究的目的是开发一种体外测定方法，以预测临床环境中含硫醇药物降低tHcy的功效。该测定法用于测试N-乙酰半胱氨酸（NAC），mesna，卡托普利，二巯基琥珀酸（DMSA）和青霉素的作用。将Hcy体外添加到健康受试者的血浆中（n = 6），并进行平衡。添加浓度的硫醇交换剂并在37℃下孵育。以选定的间隔移出等分试样，并测定游离Hcy。梅斯纳，卡托普利和NAC导致游离Hcy浓度依赖性增加。三百微摩尔美司康和卡托普利的效果比等摩尔NAC更好，游离Hcy分别提高了33.9 +/- 5.0％和32.0 +/- 2.6％，而NAC则为22.3 +/- 2.4％，p <0.001。我们的体外结果表明，mesna，卡托普利和NAC与共价结合的Hcy有效交换。该测定法可作为新型降低tHcy疗法的筛选工具，并应节省阴性试验的费用。

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